
15
The number of patients who experienced, as a first event, death due to PAH or hospitalisation for PAH
up to end of treatment was 102 (17.8%) in the selexipag group and 137 (23.5%) in the placebo group.
Death due to PAH as a component of the endpoint was observed in 16 (2.8%) patients on selexipag
and 14 (2.4%) on placebo. Hospitalisation for PAH was observed in 86 (15.0%) patients on selexipag
and 123 (21.1%) patients on placebo. Selexipag reduced the risk of hospitalisation for PAH as a first
outcome event compared to placebo (HR 0.67, 99% CI: 0.46, 0.98; one-sided log-rank p =0.04).
The total number of deaths of all causes up to study closure was 100 (17.4%) for the selexipag group
and 105 (18.0%) for the placebo group (HR 0.97, 99% CI: 0.68, 1.39). The number of deaths due to
PAH up to study closure was 70 (12.2%) for the selexipag group and 83 (14.3%) for the placebo
group.
Symptomatic endpoints
Exercise capacity was evaluated as a secondary endpoint. Median 6MWD at baseline was 376 m
(range: 90–482 m) and 369 m (range: 50–515 m) in selexipag patients and placebo patients,
respectively. Treatment with selexipag resulted in a placebo-corrected median effect on 6MWD
measured at trough (i.e., approximately 12 h post-dose) of 12 m at Week 26 (99% CI: 1, 24 m;
one-sided p value =0.0027). In patients without concurrent PAH-specific therapy, the
placebo-corrected treatment effect measured at trough was 34 m (99% CI: 10, 63 m).
Quality of life was assessed in a subset of patients in the GRIPHON study using the Cambridge
Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire. There was no significant
treatment effect from baseline to Week 26.
Long-term data in PAH
Patients enrolled into the pivotal study (GRIPHON) were eligible to enter a long-term open-label
extension study. A total of 574 patients were treated with selexipag in the GRIPHON study; of these,
330 patients continued selexipag treatment in the open-label extension study. The median follow-up
duration was 4.5 years and the median exposure to selexipag was 3 years. During the follow-up, at
least one other PAH -medicinal product was added to selexipag in 28.4% of the patients. However,
most of the treatment exposure (86.3%) in all of the 574 patients was accumulated without addition of
any new PAH medicinal product.Kaplan-Meier estimates of survival of these 574patients across the
GRIPHON and the long-term extension study at 1, 2, 5 and 7 years were 92%, 85%, 71%, and 63%,
respectively.Survival at 1, 2, 5, and 7 years for 273 patients of WHO FC II at baseline of the pivotal
study were 97%, 91%, 80% and 70%, respectively, and for 294 patients of WHO FC III at baseline
were 88%, 80%, 62% and 56%, respectively. Given that additional PAH treatment was initiated in a
small proportion of patients and that there was no control group in the extension study, the survival
benefit of selexipag cannot be confirmed from these data.
Initial triple combination treatment with selexipag, macitentan and tadalafil in newly diagnosed PAH
patients
In a double blind, placebo-controlled study, a total of 247 newly diagnosed PAH patients were
randomised to evaluate the treatment effect of initial triple (selexipag, macitentan and tadalafil)
(N =123) versus initial double (placebo, macitentan and tadalafil) (N =124) therapy.
The primary endpoint, change from baseline in pulmonary vascular resistance (PVR) at Week 26, did
not show a statistically significant difference between the groups, while showing animprovement
from baseline in both treatment groups (relative reduction by 54% in the initial triple therapy group vs
52% in the initial double therapy group).
Over a median follow-up of 2 years, 4 (3.4%) patients in the triple therapy group and 12 (9.4%)
patients in the double therapy group died.
Paediatric population
Interim efficacy and safety in paediatric patients with PAH (SALTO)
The efficacy and safety in paediatric patients aged ≥ 2 to < 18 years with PAH was evaluated in a
descriptive manner in a multi-centre, randomised, double-blind, placebo-controlled, parallel-group,
phase 3 study (SALTO). A total of 138 patients were randomised 1:1 to receive either selexipag